Pharmacological management of relapsed/refractory NSCLC with chemical drugs

ABSTRACT

Introduction: Lung cancer is the leading cause of cancer death in both genders. In the early stages the disease is asymptomatic and most patients appear with metastasis at the time of the diagnosis. The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements has changed the treatment landscape and has improved the prognosis of lung cancer patients. Inevitably, all patients initially treated with either chemotherapy or targeted therapies develop resistance and require a second-line therapeutic approach.

Areas covered: In this review we are discussing the current treatment of relapsed or refractory lung cancer. We have thoroughly searched the literature (Pubmed) the last five years for studies or reviews published on the issue of second-line therapy in lung cancer using as key words, lung cancer, relapse, EGFR mutations, ALK rearrangements, chemotherapy and immunotherapy

Expert opinion: The prognosis of lung cancer has been radically improved. Due to the recent development of checkpoint inhibitors, this also occurs for patients whose tumor’s are not driven by a genetic alteration and who, until recently, derived only minimal benefit from chemotherapy.

KEYWORDS:

• ALK
• driver oncogenes
• EGFR
• immunotherapy
• lung cancer
• relapse

Article highlights

• Lung cancer patients usually present at diagnosis with metastatic disease.

• The prognosis of stage IV non-small cell lung cancer has been radically improved due to the utilization of targeted therapies and immunotherapy.

• Most lung cancer patients develop resistance to first-line therapy (chemotherapy or targeted therapies) within a period of 4-10 months.

• Next generation targeted therapies, combined chemotherapy with antiangiogenic agents and immune checkpoint inhibitors are the current therapeutic approaches for the second-line therapy of lung cancer patients, depending on the histology and the molecular genotype of the disease.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was funded by La Caixa Foundation and Red Tematica de Investigacion Cooperativa en Cancer (RTICC; grant RD12/0036/0072)